title: Presynaptic CLC-3 determines quantal size of inhibitory transmission in the hippocampus.
abstract: The absence of the chloride channel CLC-3 in Clcn3(-/-) mice results in hippocampal degeneration with a distinct temporal-spatial sequence that resembles neuronal loss in temporal lobe epilepsy. We examined how the loss of CLC-3 might affect GABAergic synaptic transmission in the hippocampus. An electrophysiological study of synaptic function in hippocampal slices taken from Clcn3(-/-) mice before the onset of neurodegeneration revealed a substantial decrease in the amplitude and frequency of miniature inhibitory postsynaptic currents compared with those in wild-type slices. We found that CLC-3 colocalized with the vesicular GABA transporter VGAT in the CA1 region of the hippocampus. Acidification of inhibitory synaptic vesicles induced by Cl(-) showed a marked dependence on CLC-3 expression. The decrease in inhibitory transmission in Clcn3(-/-) mice suggests that the neurotransmitter loading of synaptic vesicles was reduced, which we attribute to defective vesicular acidification. Our observations extend the role of Cl(-) in inhibitory transmission from that of a postsynaptic permeant species to a presynaptic regulatory element.
authors.affiliation: Department of Neurobiology, Pharmacology and Physiology, University of Chicago, Chicago, Illinois, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Riazanski
authors.forename: Ludmila V
authors.initials: LV
authors.lastname: Deriy
authors.forename: Pavel D
authors.initials: PD
authors.lastname: Shevchenko
authors.forename: Brandy
authors.initials: B
authors.lastname: Le
authors.forename: Erwin A
authors.initials: EA
authors.lastname: Gomez
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Nelson
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism / Q000648:ultrastructure; D018118:Chloride Channels / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism* / Q000648:ultrastructure; D006863:Hydrogen-Ion Concentration; D053444:Inhibitory Postsynaptic Potentials / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009433:Neural Inhibition / Q000235:genetics / Q000502:physiology*; D009924:Organ Culture Techniques; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000235:genetics*; D013572:Synaptic Vesicles / Q000378:metabolism / Q000648:ultrastructure; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D018118:Chloride Channels; C115376:ClC-3 channel; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C492244:Viaat protein, mouse; D005680:gamma-Aminobutyric Acid